Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derive...Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of opt...Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.展开更多
Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological prop...Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.展开更多
BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and proced...BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and procedural outcomes in PEVI.METHODS A prospective observational study was performed in 186 consecutive patients(65±12 years)at an academic medical center from January 2019 to April 2020(mean follow-up of 3.9±3.6 months)comparing the gender radiation disparity and outcomes of PEVI(n=147 underwent intervention,79.0%).Groups were divided into women(n=99,53.2%)and men(n=87,48.4%).Primary endpoints included air kerma,dose area product(DAP),fluoroscopy time,and contrast use.Secondary endpoints included all-cause mortality,acute myocardial infarction,acute kidney injury,stroke,repeat revascularization,major adverse limb event,and the composite of complications.RESULTS Men showed increased DAP compared with women(15221.2±25858.5µGy×m^(2) vs 9251.7±9555.3µGy×m^(2),P=0.047),but no significant difference in air kerma or any other primary endpoints.In the secondary endpoints,no significant diffe-rence was found between gender.CONCLUSION Men had increased DAP indicating more radiation absorption in the exposed area.Gender outcomes showed no difference in complications.Thus,PEVI can be safely performed in men or women.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as L...Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as LI-RADS)classi-fication.This review synthesized published data on the integration of machine learning and deep learning techniques into CEUS,revealing that AI algorithms can improve the detection and quantification of contrast enhancement patterns.Such improvements led to more consistent LI-RADS categorization,reduced interoperator variability,and enabled real-time analysis that streamlined work-flow.The enhanced sensitivity of AI tools facilitated better differentiation between benign and malignant lesions,ultimately optimizing patient management.These advances suggest that AI-augmented CEUS could transform liver imaging by providing rapid,reliable,and objective assessments.However,the review also highlighted the need for further large-scale,multicenter studies to fully validate these findings and ensure the safe integration of AI into routine clinical practice.INTRODUCTION International hepatology society guidelines have established contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging(MRI)as the imaging modalities of choice for diagnosing hepatocellular carcinoma(HCC)lesions larger than 1 cm.MRI remains the gold standard for detecting small HCC nodules in cirrhotic livers due to its superior soft-tissue contrast and functional imaging capabilities.However,early or atypical presentations remain challenging for differential diagnosis,staging,and treatment planning.In these scenarios contrast-enhanced ultrasonography(CEUS)is a valuable second-line tool,offering real-time,radiation-free evaluation and repeatability for follow-up.A recent meta-analysis of head-to-head studies reported comparable diagnostic performance between CEUS and CT/MRI with pooled sensitivities and specificities of 0.67/0.88 for CEUS vs 0.60/0.98 for CT/MRI in non-HCC malignancies,and similar specificities for HCC diagnosis(0.70 for CEUS vs 0.59 for CT;0.81 for CEUS vs 0.79 for MRI)[1].Given the limitations of individual imaging modalities,hybrid techniques and multimodal approaches are gaining traction for improving lesion detection,especially in cases where standard methods fall short.Artificial intelligence(AI)has emerged as a powerful tool in medical imaging,enhancing diagnostic accuracy and reliability across platforms.In CEUS liver imaging dynamic enhancement patterns often challenge consistent interpretation across observers.AI holds particular promise for standardizing assessments.The growing complexity of liver tumor evaluation has also driven interest in approaches that integrate serum bio-markers with advanced imaging.However,no single strategy currently meets all the diagnostic and prognostic re-quirements.Recent studies highlighted the potential of AI to bridge this gap by enabling precise image interpretation and facilitating the integration of heterogeneous clinical and imaging data[2].Altogether the convergence of CEUS with AI and radiomics offers a dynamic,quantitative,and potentially reproducible paradigm for liver lesion assessment,comple-menting traditional imaging methods.This review aimed to provide an overview of current advances in AI-driven CEUS for liver lesion assessment with a particular focus on automated Liver Imaging Reporting and Data System(LI-RADS)classification,radiomics-based models,and future clinical integration.While another recent systematic review[3]provided a comprehensive analysis of AI applications in CEUS,our approach offers a targeted perspective,emphasizing LI-RADS-centered scoring,automated lesion characterization,and clinical utility,particularly in the context of HCC diagnosis and management.In the methodological process of this narrative mini-review,the literature selection was primarily based on targeted PubMed searches.ChatGPT-4o(OpenAI)[4]was employed to assist in refining query parameters and identifying relevant,up-to-date peer-reviewed sources on CEUS-based AI applications.展开更多
Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in m...Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in medical treatment have created a shift in cirrhosis management.Various causes,including hepatitis viruses,alcohol consumption,and fatty liver disease,contribute to cirrhosis and are closely linked to liver cancer.The disease develops through hepatocyte necrosis and regeneration,resulting in fibrosis and sinusoidal capillarization,leading to portal hypertension and complications such as ascites,hepatic encephalopathy,and organ dysfunction.Cirrhosis also holds an increased risk of hepatocellular carcinoma.Diagnosing cirrhosis involves assessing fibrosis scores through blood tests and measuring liver stiffness through elastography.Liver transplantation is the definitive treatment for endstage liver disease and acute liver failure.展开更多
Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features ...Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features such as trailers and posters,the text-based classification remains underexplored despite its accessibility and semantic richness.This paper introduces the Genre Attention Model(GAM),a deep learning architecture that integrates transformer models with a hierarchical attention mechanism to extract and leverage contextual information from movie plots formulti-label genre classification.In order to assess its effectiveness,we assessmultiple transformer-based models,including Bidirectional Encoder Representations fromTransformers(BERT),ALite BERT(ALBERT),Distilled BERT(DistilBERT),Robustly Optimized BERT Pretraining Approach(RoBERTa),Efficiently Learning an Encoder that Classifies Token Replacements Accurately(ELECTRA),eXtreme Learning Network(XLNet)and Decodingenhanced BERT with Disentangled Attention(DeBERTa).Experimental results demonstrate the superior performance of DeBERTa-based GAM,which employs a two-tier hierarchical attention mechanism:word-level attention highlights key terms,while sentence-level attention captures critical narrative segments,ensuring a refined and interpretable representation of movie plots.Evaluated on three benchmark datasets Trailers12K,Large Movie Trailer Dataset-9(LMTD-9),and MovieLens37K.GAM achieves micro-average precision scores of 83.63%,83.32%,and 83.34%,respectively,surpassing state-of-the-artmodels.Additionally,GAMis computationally efficient,requiring just 6.10Giga Floating Point Operations Per Second(GFLOPS),making it a scalable and cost-effective solution.These results highlight the growing potential of text-based deep learning models in genre classification and GAM’s effectiveness in improving predictive accuracy while maintaining computational efficiency.With its robust performance,GAM offers a versatile and scalable framework for content recommendation,film indexing,and media analytics,providing an interpretable alternative to traditional audiovisual-based classification techniques.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
Through the specific examples of two very different metropoles,not compared but evoked,New York City and Bordeaux Métropole,since globalization from mid-19th and to the beginning of the 21st century,we can observ...Through the specific examples of two very different metropoles,not compared but evoked,New York City and Bordeaux Métropole,since globalization from mid-19th and to the beginning of the 21st century,we can observe how metropolitan flows acceleration change cities and citizens heritages.How can we achieve metropolization and globalization of our cities?展开更多
The role of endoscopic retrograde cholangiopancreatography(ERCP) has dramatically changed in the last years, mainly into that of a therapeutic procedure. The treatment of benign biliary disease, like "difficult&q...The role of endoscopic retrograde cholangiopancreatography(ERCP) has dramatically changed in the last years, mainly into that of a therapeutic procedure. The treatment of benign biliary disease, like "difficult"choledocolithiasis, with endoscopic papillary large balloon dilation combined with endoscopic sphinterotomy has proven an effective and safe technique.Moreover, safety in ERCP has improved as well, with the prevention of postERCP pancreatitis and patient-to-patient transmission of infections. The advent of self-expandable metal stenting has radically changed the management of biliopancreatic malignant strictures, while the role for therapy of benign strictures is still controversial. In addition, cholangioscopy(though the direct visualization of the biliopancreatic ductal system) has allowed for characterization of indeterminate biliary strictures and facilitated rescue therapy of large biliary stones deemed removable. Encouraging data from tissue ablation techniques, such as photodynamic therapy and radiofrequency ablation, need to be confirmed by large sample size clinical controlled trials. On the other hand, we have no drug-coated stents yet available to implant and evidence for the use of biodegradable stents is still weak. The competency and privileging of ERCP and endoscopic ultrasonography have been analyzed longer but the switch between the two procedures, at the same time, is becoming ordinary; as such, the endoscopist interested in this field should undergo parallel edification through training plans. Finally, the American Society for Gastrointestinal Endoscopy's statement on non-anesthesiologist administration of propofol for gastrointestinal endoscopy is not actually endorsed by the European Society of Anaesthesiology,having many medical-legal implications in some European countries.展开更多
The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts...The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.展开更多
Aqueous Zn-iodine batteries(ZIBs)face the formidable challenges towards practical implementation,including metal corrosion and rampant dendrite growth on the Zn anode side,and shuttle effect of polyiodide species from...Aqueous Zn-iodine batteries(ZIBs)face the formidable challenges towards practical implementation,including metal corrosion and rampant dendrite growth on the Zn anode side,and shuttle effect of polyiodide species from the cathode side.These challenges lead to poor cycle stability and severe self-discharge.From the fabrication and cost point of view,it is technologically more viable to deploy electrolyte engineering than electrode protection strategies.More importantly,a synchronous method for modulation of both cathode and anode is pivotal,which has been often neglected in prior studies.In this work,cationic poly(allylamine hydrochloride)(Pah^(+))is adopted as a low-cost dual-function electrolyte additive for ZIBs.We elaborate the synchronous effect by Pah^(+)in stabilizing Zn anode and immobilizing polyiodide anions.The fabricated Zn-iodine coin cell with Pah^(+)(ZnI_(2) loading:25 mg cm^(−2))stably cycles 1000 times at 1 C,and a single-layered 3.4 cm^(2) pouch cell(N/P ratio~1.5)with the same mass loading cycles over 300 times with insignificant capacity decay.展开更多
Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment ...Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.展开更多
Lymphedema,particularly in its advanced stages,presents significant challenges in treatment,often necessitating a combination of therapies to manage symptoms effectively and improve patient outcomes.This article revie...Lymphedema,particularly in its advanced stages,presents significant challenges in treatment,often necessitating a combination of therapies to manage symptoms effectively and improve patient outcomes.This article reviews the findings of Wang et al,regarding the use of lymphovenous anastomosis and complex decongestive therapy in treating severe,deformed stage III lymphedema with recurrent infections.The case report details the promising results achieved through this combined therapy,highlighting substantial reductions in limb volume and the complete resolution of recurrent lymphangitis.The patient experienced notable improvements in weight loss,physical function,and quality of life.Despite its strengths,the study has several limitations.It lacks specific details on the types of lymphovenous anastomoses performed and complex decongestive therapy protocols,such as frequency and adherence,making reproducibility difficult.The short follow-up period of six months limits understanding of long-term efficacy,and more consistent reporting of key metrics such as weight loss and body mass index would enhance outcome assessments.This article emphasizes the importance of integrating minimally invasive surgical techniques with conservative therapies to address both the symptoms and underlying causes of lymphedema.Further research is essential to standardize protocols and refine combined treatment strategies.展开更多
BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
Computer analysis of electrocardiograms(ECGs)was introduced more than 50 years ago,with the aim to improve efficiency and clinical workflow.[1,2]However,inaccuracies have been documented in the literature.[3,4]Researc...Computer analysis of electrocardiograms(ECGs)was introduced more than 50 years ago,with the aim to improve efficiency and clinical workflow.[1,2]However,inaccuracies have been documented in the literature.[3,4]Research indicates that emergency department(ED)clinician interruptions occur every 4-10 min,which is significantly more common than in other specialties.[5]This increases the cognitive load and error rates and impacts patient care and clinical effi ciency.[1,2,5]De-prioritization protocols have been introduced in certain centers in the United Kingdom(UK),removing the need for clinician ECG interpretation where ECGs have been interpreted as normal by the machine.展开更多
Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal funct...Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.展开更多
基金supported by project Emerging Infectious Diseases One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,INF-ACT,Spoke 1 and Spoke 5,Project number PE00000007,CUP B53C20040570005(to PP and DN).
文摘Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
基金supported by a grant from the Russian Science Foundation,No.23-75-10041(to MY)。
文摘Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.
基金supported by the Shenzhen Hong Kong Joint Funding Project,No.SGDX20230116093645007(to LY)the Shenzhen Science and Technology Innovation Committee International Cooperation Project,No.GJHZ20200731095608025(to LY)+7 种基金Shenzhen Development and Reform Commission’s Intelligent Diagnosis,Treatment and Prevention of Adolescent Spinal Health Public Service Platform,No.S2002Q84500835(to LY)Shenzhen Medical Research Fund,No.B2303005(to LY)Team-based Medical Science Research Program,No.2024YZZ02(to LY)Zhejiang Provincial Natural Science Foundation of China,No.LWQ20H170001(to RL)Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324103010029(to BY)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project,Nos.2023yjlcyj029(to BY),2023yjlcyj021(to LL)Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110679(to LL)China Postdoctoral Science Foundation,No.2022M722203(to GL).
文摘Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.
文摘BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and procedural outcomes in PEVI.METHODS A prospective observational study was performed in 186 consecutive patients(65±12 years)at an academic medical center from January 2019 to April 2020(mean follow-up of 3.9±3.6 months)comparing the gender radiation disparity and outcomes of PEVI(n=147 underwent intervention,79.0%).Groups were divided into women(n=99,53.2%)and men(n=87,48.4%).Primary endpoints included air kerma,dose area product(DAP),fluoroscopy time,and contrast use.Secondary endpoints included all-cause mortality,acute myocardial infarction,acute kidney injury,stroke,repeat revascularization,major adverse limb event,and the composite of complications.RESULTS Men showed increased DAP compared with women(15221.2±25858.5µGy×m^(2) vs 9251.7±9555.3µGy×m^(2),P=0.047),but no significant difference in air kerma or any other primary endpoints.In the secondary endpoints,no significant diffe-rence was found between gender.CONCLUSION Men had increased DAP indicating more radiation absorption in the exposed area.Gender outcomes showed no difference in complications.Thus,PEVI can be safely performed in men or women.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
文摘Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as LI-RADS)classi-fication.This review synthesized published data on the integration of machine learning and deep learning techniques into CEUS,revealing that AI algorithms can improve the detection and quantification of contrast enhancement patterns.Such improvements led to more consistent LI-RADS categorization,reduced interoperator variability,and enabled real-time analysis that streamlined work-flow.The enhanced sensitivity of AI tools facilitated better differentiation between benign and malignant lesions,ultimately optimizing patient management.These advances suggest that AI-augmented CEUS could transform liver imaging by providing rapid,reliable,and objective assessments.However,the review also highlighted the need for further large-scale,multicenter studies to fully validate these findings and ensure the safe integration of AI into routine clinical practice.INTRODUCTION International hepatology society guidelines have established contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging(MRI)as the imaging modalities of choice for diagnosing hepatocellular carcinoma(HCC)lesions larger than 1 cm.MRI remains the gold standard for detecting small HCC nodules in cirrhotic livers due to its superior soft-tissue contrast and functional imaging capabilities.However,early or atypical presentations remain challenging for differential diagnosis,staging,and treatment planning.In these scenarios contrast-enhanced ultrasonography(CEUS)is a valuable second-line tool,offering real-time,radiation-free evaluation and repeatability for follow-up.A recent meta-analysis of head-to-head studies reported comparable diagnostic performance between CEUS and CT/MRI with pooled sensitivities and specificities of 0.67/0.88 for CEUS vs 0.60/0.98 for CT/MRI in non-HCC malignancies,and similar specificities for HCC diagnosis(0.70 for CEUS vs 0.59 for CT;0.81 for CEUS vs 0.79 for MRI)[1].Given the limitations of individual imaging modalities,hybrid techniques and multimodal approaches are gaining traction for improving lesion detection,especially in cases where standard methods fall short.Artificial intelligence(AI)has emerged as a powerful tool in medical imaging,enhancing diagnostic accuracy and reliability across platforms.In CEUS liver imaging dynamic enhancement patterns often challenge consistent interpretation across observers.AI holds particular promise for standardizing assessments.The growing complexity of liver tumor evaluation has also driven interest in approaches that integrate serum bio-markers with advanced imaging.However,no single strategy currently meets all the diagnostic and prognostic re-quirements.Recent studies highlighted the potential of AI to bridge this gap by enabling precise image interpretation and facilitating the integration of heterogeneous clinical and imaging data[2].Altogether the convergence of CEUS with AI and radiomics offers a dynamic,quantitative,and potentially reproducible paradigm for liver lesion assessment,comple-menting traditional imaging methods.This review aimed to provide an overview of current advances in AI-driven CEUS for liver lesion assessment with a particular focus on automated Liver Imaging Reporting and Data System(LI-RADS)classification,radiomics-based models,and future clinical integration.While another recent systematic review[3]provided a comprehensive analysis of AI applications in CEUS,our approach offers a targeted perspective,emphasizing LI-RADS-centered scoring,automated lesion characterization,and clinical utility,particularly in the context of HCC diagnosis and management.In the methodological process of this narrative mini-review,the literature selection was primarily based on targeted PubMed searches.ChatGPT-4o(OpenAI)[4]was employed to assist in refining query parameters and identifying relevant,up-to-date peer-reviewed sources on CEUS-based AI applications.
文摘Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in medical treatment have created a shift in cirrhosis management.Various causes,including hepatitis viruses,alcohol consumption,and fatty liver disease,contribute to cirrhosis and are closely linked to liver cancer.The disease develops through hepatocyte necrosis and regeneration,resulting in fibrosis and sinusoidal capillarization,leading to portal hypertension and complications such as ascites,hepatic encephalopathy,and organ dysfunction.Cirrhosis also holds an increased risk of hepatocellular carcinoma.Diagnosing cirrhosis involves assessing fibrosis scores through blood tests and measuring liver stiffness through elastography.Liver transplantation is the definitive treatment for endstage liver disease and acute liver failure.
基金would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support(QU-APC-2025).
文摘Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features such as trailers and posters,the text-based classification remains underexplored despite its accessibility and semantic richness.This paper introduces the Genre Attention Model(GAM),a deep learning architecture that integrates transformer models with a hierarchical attention mechanism to extract and leverage contextual information from movie plots formulti-label genre classification.In order to assess its effectiveness,we assessmultiple transformer-based models,including Bidirectional Encoder Representations fromTransformers(BERT),ALite BERT(ALBERT),Distilled BERT(DistilBERT),Robustly Optimized BERT Pretraining Approach(RoBERTa),Efficiently Learning an Encoder that Classifies Token Replacements Accurately(ELECTRA),eXtreme Learning Network(XLNet)and Decodingenhanced BERT with Disentangled Attention(DeBERTa).Experimental results demonstrate the superior performance of DeBERTa-based GAM,which employs a two-tier hierarchical attention mechanism:word-level attention highlights key terms,while sentence-level attention captures critical narrative segments,ensuring a refined and interpretable representation of movie plots.Evaluated on three benchmark datasets Trailers12K,Large Movie Trailer Dataset-9(LMTD-9),and MovieLens37K.GAM achieves micro-average precision scores of 83.63%,83.32%,and 83.34%,respectively,surpassing state-of-the-artmodels.Additionally,GAMis computationally efficient,requiring just 6.10Giga Floating Point Operations Per Second(GFLOPS),making it a scalable and cost-effective solution.These results highlight the growing potential of text-based deep learning models in genre classification and GAM’s effectiveness in improving predictive accuracy while maintaining computational efficiency.With its robust performance,GAM offers a versatile and scalable framework for content recommendation,film indexing,and media analytics,providing an interpretable alternative to traditional audiovisual-based classification techniques.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
基金supported by European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
文摘Through the specific examples of two very different metropoles,not compared but evoked,New York City and Bordeaux Métropole,since globalization from mid-19th and to the beginning of the 21st century,we can observe how metropolitan flows acceleration change cities and citizens heritages.How can we achieve metropolization and globalization of our cities?
文摘The role of endoscopic retrograde cholangiopancreatography(ERCP) has dramatically changed in the last years, mainly into that of a therapeutic procedure. The treatment of benign biliary disease, like "difficult"choledocolithiasis, with endoscopic papillary large balloon dilation combined with endoscopic sphinterotomy has proven an effective and safe technique.Moreover, safety in ERCP has improved as well, with the prevention of postERCP pancreatitis and patient-to-patient transmission of infections. The advent of self-expandable metal stenting has radically changed the management of biliopancreatic malignant strictures, while the role for therapy of benign strictures is still controversial. In addition, cholangioscopy(though the direct visualization of the biliopancreatic ductal system) has allowed for characterization of indeterminate biliary strictures and facilitated rescue therapy of large biliary stones deemed removable. Encouraging data from tissue ablation techniques, such as photodynamic therapy and radiofrequency ablation, need to be confirmed by large sample size clinical controlled trials. On the other hand, we have no drug-coated stents yet available to implant and evidence for the use of biodegradable stents is still weak. The competency and privileging of ERCP and endoscopic ultrasonography have been analyzed longer but the switch between the two procedures, at the same time, is becoming ordinary; as such, the endoscopist interested in this field should undergo parallel edification through training plans. Finally, the American Society for Gastrointestinal Endoscopy's statement on non-anesthesiologist administration of propofol for gastrointestinal endoscopy is not actually endorsed by the European Society of Anaesthesiology,having many medical-legal implications in some European countries.
文摘The kidneys play a critical role in maintaining glucose homeostasis.Under normal renal tubular function,most of the glucose filtered from the glomeruli is re-absorbed in the proximal tubules,leaving only trace amounts in the urine.Glycosuria can occur as a symptom of generalized proximal tubular dysfunction or when the reabsorption threshold is exceeded or the glucose threshold is reduced,as seen in familial renal glycosuria(FRG).FRG is characterized by persistent glycosuria despite normal blood glucose levels and tubular function and is primarily associated with mutations in the sodium/glucose cotransporter 5A2 gene,which encodes the sodium-glucose cotransporter(SGLT)2.Inhibiting SGLTs has been proposed as a novel treatment strategy for diabetes,and since FRG is often considered an asymptomatic and benign condition,it has inspired preclinical and clinical studies using SGLT2 inhibitors in type 2 diabetes.However,patients with FRG may exhibit clinical features such as lower body weight or height,altered systemic blood pressure,diaper dermatitis,amino-aciduria,decreased serum uric acid levels,and hypercalciuria.Further research is needed to fully understand the pathophysiology,molecular genetics,and clinical manifestations of renal glucosuria.
基金supported by the financial support from the National Research Foundation,Singapore,under its Singapore-China Joint Flagship Project(Clean Energy).
文摘Aqueous Zn-iodine batteries(ZIBs)face the formidable challenges towards practical implementation,including metal corrosion and rampant dendrite growth on the Zn anode side,and shuttle effect of polyiodide species from the cathode side.These challenges lead to poor cycle stability and severe self-discharge.From the fabrication and cost point of view,it is technologically more viable to deploy electrolyte engineering than electrode protection strategies.More importantly,a synchronous method for modulation of both cathode and anode is pivotal,which has been often neglected in prior studies.In this work,cationic poly(allylamine hydrochloride)(Pah^(+))is adopted as a low-cost dual-function electrolyte additive for ZIBs.We elaborate the synchronous effect by Pah^(+)in stabilizing Zn anode and immobilizing polyiodide anions.The fabricated Zn-iodine coin cell with Pah^(+)(ZnI_(2) loading:25 mg cm^(−2))stably cycles 1000 times at 1 C,and a single-layered 3.4 cm^(2) pouch cell(N/P ratio~1.5)with the same mass loading cycles over 300 times with insignificant capacity decay.
基金supported by #NEXTGENERATIONEU(NGEU)and funded by the Ministry of University and Research(MUR),National Recovery and Resilience Plan(NRRP),project MNESYS(PE0000006)-(DN.155311.10.2022)supported by Sapienza Grant 2021(RM12117A60BDF685).
文摘Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.
文摘Lymphedema,particularly in its advanced stages,presents significant challenges in treatment,often necessitating a combination of therapies to manage symptoms effectively and improve patient outcomes.This article reviews the findings of Wang et al,regarding the use of lymphovenous anastomosis and complex decongestive therapy in treating severe,deformed stage III lymphedema with recurrent infections.The case report details the promising results achieved through this combined therapy,highlighting substantial reductions in limb volume and the complete resolution of recurrent lymphangitis.The patient experienced notable improvements in weight loss,physical function,and quality of life.Despite its strengths,the study has several limitations.It lacks specific details on the types of lymphovenous anastomoses performed and complex decongestive therapy protocols,such as frequency and adherence,making reproducibility difficult.The short follow-up period of six months limits understanding of long-term efficacy,and more consistent reporting of key metrics such as weight loss and body mass index would enhance outcome assessments.This article emphasizes the importance of integrating minimally invasive surgical techniques with conservative therapies to address both the symptoms and underlying causes of lymphedema.Further research is essential to standardize protocols and refine combined treatment strategies.
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
文摘Computer analysis of electrocardiograms(ECGs)was introduced more than 50 years ago,with the aim to improve efficiency and clinical workflow.[1,2]However,inaccuracies have been documented in the literature.[3,4]Research indicates that emergency department(ED)clinician interruptions occur every 4-10 min,which is significantly more common than in other specialties.[5]This increases the cognitive load and error rates and impacts patient care and clinical effi ciency.[1,2,5]De-prioritization protocols have been introduced in certain centers in the United Kingdom(UK),removing the need for clinician ECG interpretation where ECGs have been interpreted as normal by the machine.
基金supported by the National Natural Science Foundation of China,No.82201582(to QT)Scientific and Technological Research Program of Chongqing Municipal Education Commission,No.KJQN202200457(to QT)+3 种基金General Project of Changqing Natural Science Foundation,No.cstc2021jcyjmsxmX0442(to ZL)CQMU Program for Youth Innovation in Future Medicine,No.W0044(to ZD and GH)Direct Research Project for PhD of Chongqing,No.CSTB2022BSXM-JCX0051(to ZL)the Project of the Top-Notch Talent Cultivation Program For the Graduate Students of Chongqing Medical University,No.BJRC202310(to CG)。
文摘Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.
